洛伐他汀、辛伐他汀和阿托伐他汀对大鼠肝肾毒性的比较研究CSCD

目的观察洛伐他汀、辛伐他汀和阿托伐他汀连续给药1个月对大鼠肝肾的毒性作用,为临床用药安全性提供数据支持。方法SD大鼠分别灌胃给予洛伐他汀、辛伐他汀和阿托伐他汀(68.5和205.5 mg/kg·bw),给药1次/d,28 d后测血清中丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、碱性磷酸酶(ALP)、肌酐(CRE)和尿氮(BUN)。取肝和肾,甲醛固定,苏木素-伊红(HE)染色,光学显微镜观察肝和肾组织的病理结构变化。结果辛伐他汀和阿托伐他汀的主要毒性反应剂量在205.5 mg/kg·bw,给药后大鼠出现了脱毛、腹泻等表现,血液生化检查显示ALP、ALT和AST明显升高。病理结果表明,辛伐他汀高剂量组、阿托伐他汀高剂量组和阿托伐他汀低剂量组对大鼠肝均有一定程度的毒性损伤作用。结论阿托伐他汀和辛伐他汀高剂量组可引起大鼠肝组织的病理损伤,ALP、ALT和AST明显升高;洛伐他汀高剂量组对大鼠肝肾毒性作用不明显。根据肝病理毒性由弱到强排序为:洛伐他汀高剂量<辛伐他汀高剂量组<阿托伐他汀低剂量组<阿托伐他汀高剂量组。     

复方鳖甲软肝注射剂对大鼠肝硬化的防治作用

目的探讨由丝瓜络和鳖甲经适当配伍、萃取制成的复方鳖甲软肝注射剂对Wistar大鼠肝硬化的预防和治疗作用。方法通过大鼠皮下注射40%四氯化碳菜籽油溶液、自由饮用10%乙醇和高脂低蛋白饲料构建大鼠肝硬化模型,探讨该注射剂在肝硬化造模过程中及造模成功后对大鼠血液中白蛋白(A)、球蛋白(G)、A/G、丙氨酸氨基转氨酶(ALT)、天门冬氨酸氨基转氨酶(AST)、透明质酸酶(HA)、肝指数、脾指数、肝组织病理、体重增长、死亡率以及生存状态等的影响。结果与模型组相比,在预防阶段该注射剂能显著升高A和G;显著降低ALT、AST、HA、肝指数及死亡率;注射剂组大鼠的平均体重增长较模型组明显;肝脏切片显示:注射剂组大鼠的肝脏病变程度也显著轻于模型组。治疗18 d后与对照组相比,该注射剂可显著降低AST、ALT,并逆转A/G倒置;治疗组的肝脏纤维增生、炎细胞浸润、胞浆凝固及肝窦血管化程度较治疗对照组可明显减轻。结论该复方注射剂对肝硬化具有较好的预防作用和一定的治疗效果。     

硫代乙酰胺诱导大鼠肝纤维化模型的制备

目的:建立稳定高效的硫代乙酰胺(thioacetamide,TAA)大鼠肝纤维化模型,分析大鼠肝脏病理纤维化分级与血清检测物指标,为临床提供适用的监测手段及理论依据。方法:选取SD雄性大鼠48只,随机分为4组,即对照组(12只)、模型-Ⅰ组(12只)、模型-Ⅱ组(12只)和模型-Ⅲ组(12只)。根据大鼠体重,采用腹腔注射TAA诱导肝纤维化。按实验给定时间给药,在不同时间段内测定谷草转氨酶(AST)和谷丙转氨酶(ALT)血清浓度,并进行肝脏病理组织学检查。结果:模型-Ⅰ组大鼠死亡率为25.00%(3/12)、肝纤维化形成率为75.00%(9/12);模型-Ⅱ组大鼠死亡率为8.33%(1/12)、肝纤维化形成率为91.67%(11/12);模型-Ⅲ组肝纤维化形成率为83.33%(10/12)。各组AST和ALT血清浓度均升高,肝脏病理组织学检查发现肝组织病变。结论:本法病理组织学检查结果可靠,操作简便,适用于实验肝纤维化模型制备。     

珠子肝泰对实验性慢性肝损伤的影响

目的观察珠子肝泰合剂对慢性肝损伤的作用。方法采用适量四氯化碳(CCl4)多次注射造成慢性肝损伤模型,给予同剂量的珠子肝泰合剂,测定血清转氨酶(ALT、AST)、胆碱酯酶(CHE),肝组织匀浆ALT与CHE、谷胱苷肽(GSH)、丙二醛(MDA)、碱性磷酸酶(ALP),HE染色观察肝组织形态学。结果珠子肝泰合剂能有效地降低CCl4所致慢性肝损伤大鼠血清与匀浆ALT,升高血清CHE,降低GSH与MDA,HE显示受损的肝细胞有用药后较好的恢复作用。结论珠子肝泰合剂对皮下注射四氯化碳致大鼠慢性肝损伤具有显著的治疗作用,主要表现在能明显降低肝脏重量指数,降低ALT、AST,能升高血清白蛋白(ALB),纠正白球蛋白比(A/G),显著减轻慢性肝损伤大鼠病理损伤,提示该制剂对慢性肝损伤有保护作用。降低肝组织胶原纤维含量(胶原总数目、胶原总面积),抑制胶原纤维生成,减轻肝硬化病变。     

假淡红鹅膏对大鼠肝功能的影响

目的探讨假淡红鹅膏对SD大鼠肝功能的影响。方法对假淡红鹅膏中α-鹅膏毒肽和β-鹅膏毒肽含量测定,以SD大鼠为研究对象,用Horn法计算假淡红鹅膏的LD_(50),测定假淡红鹅膏对大鼠血清中丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)和碱性磷酸酶(ALP)水平的影响,并进行肝病理学检查。结果假淡红鹅膏(干品)的α-鹅膏毒肽和β-鹅膏毒肽含量分别为674.56和411.91 mg/kg;假淡红鹅膏雄性大鼠LD_(50)及95%可信区间(95%CI)为23.7(14.2～39.5)mg/kg,雌性大鼠的LD_(50)及95%CI为27.1(20.0～3.69)mg/kg,各假淡红鹅膏组ALT、AST和ALP较空白组均增加,且随着假淡红鹅膏剂量的增加,ALT、AST和ALP增加更明显;空白组大鼠肝组织结构清晰,无明显病变;各染毒组大鼠出现肝小叶结构紊乱、出血、肝细胞水肿和坏死,随着假淡红鹅膏剂量增加,肝病理改变越明显。结论假淡红鹅膏可以导致大鼠急性肝损伤。     

叶黄素对阿霉素所致大鼠心、肾损伤的保护作用

目的 探讨叶黄素对阿霉素所致大鼠心、肾毒性的保护作用及其机制.方法 采用单次腹腔注射阿霉素(10mg/kg)造成大鼠实验性心、肾病模型,研究注射阿霉素前、后叶黄素灌胃对大鼠血液生化学指标、组织生化指标及病理组织学的影响.结果 心、肾病模型组大鼠血清谷丙转氨酶(ALT)、谷草转氨酶(AST)、乳酸脱氢酶(LDH)、肌酸激酶(CK)、血尿素氮(BUN)、肌酐(Cr)含量均明显高于对照组,心、肾组织匀浆中丙二醛(MDA)含量显著增加,而谷胱甘肽过氧化物酶(GSH-Px)及超氧化物歧化酶(SOD)活性显著下降.叶黄素(20mg·kg-1·d-1)可降低心、肾损伤大鼠血清AST、ALT、LDH、CK、BUN及Cr水平,改善阿霉素损伤大鼠心、肾病理组织学变化,并降低心、肾组织匀浆MDA水平,提高组织GSH-Px及SOD活性.结论 叶黄素通过抗氧化作用对大鼠阿霉素心、肾损伤产生保护和治疗作用.     

病毒性肝炎患者血清ALT/AST A/G比值与病变程度的关系

目的　探讨病毒性肝炎患者的血清丙氨酸氨基转移酶 (ALT)和门冬氨酸氨基转移酶 (AST)、白蛋白 (A)和球蛋白 (G)的比值与病变程度的关系。方法　检测 42 4例肝炎患者ALT、AST、A、G及计算ALT/AST、A/G比值。结果　随着肝实质损害的加重 ,ALT/AST及A/G比值逐渐缩小 ,表现为ALT/AST与A/G呈同步变化 ,各型肝炎相应的ALT/AST及A/G比值差异有显著性 (P <0 0 1或P <0 0 5 )。结论　ALT/AST与A/G比值对判断病毒性肝炎的病情预后有一定的帮助 ,该方法简单易行     

苯甲酸阿格列汀致肝损伤

1例57岁男性2型糖尿病患者口服苯甲酸阿格列汀25 mg、1次/d, 用药前肝功能正常。服用阿格列汀25 d后, 患者出现皮肤黄染、乏力。实验室检查示总胆红素(TBil)65 μmol/L, 丙氨酸转氨酶(ALT)2 856 U/L, 天冬氨酸转氨酶(AST)1 028 U/L, 碱性磷酸酶(ALP)124 U/L。排除病毒性肝炎、自身免疫性肝病和梗阻性黄疸后, 考虑为苯甲酸阿格列汀导致的肝损伤。停用该药并给予保肝治疗。17 d后, 患者上述症状消失, 实验室检查示TBil 17 μmol/L, ALT 112 U/L, AST 30 U/L, ALP 76 U/L。     

茶黄素对高尿酸血症小鼠的降尿酸作用研究

目的研究茶黄素对高尿酸血症模型小鼠的降尿酸作用。方法采用氧嗪酸钾诱导高尿酸血症小鼠模型,茶黄素低、中、高剂量(6、20、60 mg/kg)和别嘌呤(10 mg/kg)连续ig给药7 d,检测高尿酸血症小鼠血清尿酸(UA)、尿素氮(BUN)、肌酐(CRE)、天冬氨酸氨基转氨酶(AST)、丙氨酸氨基转氨酶(ALT)水平,评价茶黄素的降尿酸作用。结果与对照组比较,模型组小鼠血清CRE、BUN、AST和ALT水平显著升高;与模型组相比,茶黄素中、高剂量组小鼠血清UA、CRE、BUN、AST、ALT水平显著降低(P<0.01)。结论茶黄素对于氧嗪酸钾诱导的高尿酸血症模型小鼠有良好的降尿酸作用。     

安神补脑液致肝损伤2例

2例患者(例1女, 49岁;例2女, 51岁)均因睡眠不佳自行口服安神补脑液10 ml、2次/d。2例患者均无合并用药。例1和例2分别在服用安神补脑液7和10 d后出现乏力、纳差, 实验室检查示丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、碱性磷酸酶(ALP)分别为1 147、1 271、215 U/L和805、333、227 U/L。停用安神补脑液并予保肝治疗7 d后, 2例患者乏力、纳差等症状得到改善, ALT、AST、ALP分别降至222、396、122 U/L和85、23、129 U/L。例1再次服用安神补脑液, 2 d后出现上腹部不适伴呕吐, ALT 409 U/L、AST 339 U/L;停用该药并给予保肝治疗近4个月后, ALT 32 U/L、AST 22 U/L, ALP 89 U/L。例2未再服用该药, 出院138天复查, ALT 39 U/L、AST 28 U/L、ALP 130 U/L。     

安络化纤丸预防大鼠酒精性脂肪肝形成的作用

目的研究安络化纤丸对大鼠酒精性脂肪肝(AFLD)形成的预防作用。方法首先经灌胃给予大鼠安络化纤丸预防性治疗4周,后用连续灌服酒精加喂以特制饲料的方法制备大鼠AFLD模型,造模成功后观察一般情况及测定血清谷丙转氨酶(ALT)、谷草转氨酶(AST)、碱性磷酸酶(AKP)、甘油三酯(TG)水平,测定肝组织匀浆TG、丙二醛(MDA)及超氧化物歧化酶(SOD)水平,并对大鼠肝脏组织作病理学检查。结果安络化纤丸可明显降低AFLD大鼠血清ALT、AST、AKP、TG水平,降低肝组织TG含量,升高肝组织SOD活性,并降低肝组织MDA水平。肝组织病理学结果表明,安络化纤丸可显著改善AFLD大鼠肝组织的病理损害。结论安络化纤丸有预防大鼠AFLD形成的作用。     

山豆根水提组分大鼠长期毒性实验研究

目的 观察连续给予山豆根水提组分导致大鼠慢性毒性的损伤表现、程度及可逆性.方法 连续27天分别给80只大鼠灌胃高、中、低剂量的山豆根水提组分样品,除观察一般状况外,检测血常规、血生化指标,剖杀大鼠,精密称取心、肝、脾、肺、肾脏,计算脏体比值,进行常规病理检查.停药后进行恢复期观察.结果 连续给予不同剂量山豆根水提组分可致使大鼠体重下降,饮食、饮水不佳;血清丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、碱性磷酸酶(ALP)增高,肝体比值升高,病理检查可见不同程度的肝损伤,对血常规无明显影响.肝毒性损伤程度与给药剂量呈现一定的剂量依赖相关性.停药后,部分病理改变不可逆.结论 山豆根水提组分长期给药的长期毒性表现为血清ALT、.AST、ALP活性及尿素氮(BuN)、肌酐(CRE)含量的变化,且部分病变为不可逆性损伤.     

Comparative evaluation of the protective effect of selenium and garlic against liver and kidney damage induced by mercury chloride in the rats

The present study was designed to compare the protective effect of selenium and garlic against liver and kidney damage induced by (ip) injection of 0.5 mg/kg mercury chloride (HgCl(2)) in rats. Thirty-six Sprague-Dawley rats were used in the present experiment and divided into six groups: one group was orally given (1 ml) saline and served as a control group; two groups of rats were given either selenium (0.1 mg/kg) or garlic (63 mg/kg) alone, once daily an oral dose for 30 successive days; other two groups of rats were given either selenium or garlic alone, once daily a dose for 15 successive days prior to HgCl(2) injection and on the next 15 successive days simultaneously with HgCl(2) injection; and the last group of rats was injected ip with HgCl(2) for 15 days and at the end of the experiment (which lasted 30 days), blood samples for the biochemical analysis were obtained from all rats after being lightly anesthetized with ether, and specimens of kidney and liver were removed and prepared for histochemical study. Computer image analysis was applied to liver and kidney tissues to evaluate the DNA density and DNA ploidy pattern in different groups. The results revealed that the rats injected with HgCl(2) showed a significant increase in levels of blood urea nitrogen (BUN), serum creatinine, alanine aminotransferase (ALT), aspartate aminotransferase (AST) by 29.3%, 62.5%, 29.46% and 30.61%, respectively, while alkaline phosphatase (ALP) showed a significant decrease by 22.6% as compared with saline control group. Rats that were given selenium in combination with the HgCl(2) injection showed a significant decrease in BUN, Serum creatinine, ALT and AST levels, while ALP was significantly increased as compared with HgCl(2) group. Also rats that were given garlic in combination with HgCl(2) injection showed a significant decrease in BUN, Serum creatinine, ALT and AST levels, although serum ALP level showed an increase as compared to HgCl(2) group. Rats that had been orally administered selenium or garlic alone did not show any significant changes in the serum level of BUN, Serum creatinine, ALT and AST but there was a significant decrease in ALP level as compared with saline control group. The cytometric results revealed that injection of HgCl(2) induced an increase in the DNA density in kidney tissues with an increase in aneuploid cells and decrease in diploid cells. However, DNA density decreased in liver tissues with mild decrease in diploid cells and little percentage of aneuploid cells. We can conclude that oral administration of either selenium or garlic produces a significant protection against liver and kidney damage induced by the HgCl(2) injection, but garlic appears to be more protective.     

细胞外信号调节激酶1/2抑制剂PD98059对弥散性血管内凝血大鼠多器官损伤的保护作用

目的:研究细胞外信号调节激酶1/2(ERK1/2)抑制剂PD98059对大鼠内毒素弥散性血管内凝血(DIC)多器官损伤的保护作用。方法:Sprague-Dawley(SD)大鼠随机分为对照组、DIC组及抑制剂组。DIC组通过腹腔注射6mg/kg脂多糖(LPS)建立内毒素DIC模型,抑制剂组腹腔注射6mg/kg LPS和10mg/kg PD98059。5h后取血,利用全自动血凝仪及生化仪检测活化部分凝血活酶时间(APTT)、纤维蛋白原(FIB)、乳酸脱氢酶(LDH)、碱性磷酸酶(ALP)、谷丙转氨酶(ALT)、谷草转氨酶(AST)、尿素(BUN)及肌酐(Cr)等指标;并留取心肝肾组织,光镜下观察其形态学变化。结果:与对照组相比:DIC组APTT、LDH、ALP、ALT、AST、BUN及Cr均延长或升高(P<0.01),FIB较对照组降低(P<0.01),心、肝、肾组织病理学检查均有明显的血管扩张充血;PD98059预防性用药后,除Cr外各指标均有明显改善(P<0.01),心、肝、肾组织血管充血减轻。结论:ERK1/2抑制剂PD98059能够减轻内毒素DIC时的多器官损伤,其机制与ERK1/2信号通路的抑制有关。     

Effect of glycine on tissue fatty acid composition in an experimental model of alcohol-induced hepatotoxicity

1. The aim of the present study was to investigate the effect of the administration of glycine, a non-essential amino acid, on blood alcohol levels and tissue fatty acid composition in experimental rats. 2. Liver cell damage was induced by the administration of ethanol (7.9 g/kg bodyweight) for 30 days by intragastric intubation. Control rats were given isocaloric glucose solution. Glycine was subsequently administered at a dose of 0.6 g/kg bodyweight every day by intragastric intubation for the next 30 days. 3. Feeding alcohol significantly elevated the activities of serum aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatases (ALP) and gamma-glutamyl transpeptidase (GGT) and altered the liver and brain fatty acid composition compared with control rats. Subsequently, glycine supplementation to alcohol-fed rats significantly lowered the activities of serum AST, ALT, ALP, GGT and normalized the liver and brain fatty acid composition compared with untreated alcohol-fed rats. 4. Thus, the present study demonstrates that oral administration of glycine confers a significant protective effect against alcohol-induced hepatotoxicity by virtue of its ability to optimize the activities of serum AST, ALT, ALP and GGT, as well as the tissue fatty acid composition.     

醒酒护肝口服液对小鼠酒精性肝损伤的保护作用简

目的评价醒酒护肝口服液对酒精性肝损伤的保护作用。方法建立小鼠急性酒精肝损伤模型,监测血中乙醇浓度,以评价醒酒护肝口服液对乙醇清除速率的作用;建立小鼠慢性酒精性肝损伤模型,以血液生化指标天门冬氨酸氨基转移酶（AST）、丙氨酸氨基转移酶（ALT）、肝指数及肝组织病理学检查评价醒酒护肝口服液的护肝作用。结果醒酒护肝口服液组小鼠血中乙醇代谢速率加快,浓度降低;药物组均可降低肝损伤小鼠AST、ALT、肝损伤评分值;与模型对照组比较,醒酒护肝口服液组A1月有显著性差异。结论醒酒护肝口服液对酒精性肝损伤有保护作用。     

Subacute toxicity of uranyl acetate in Swiss-Albino mice

Subacute effects of uranyl acetate were investigated in laboratory mice (Mus musculus, Swiss-Albino). Uranyl acetate was administrated to mice during a period of 5 days with dietary consumption ad libitum. Effects of uranyl acetate on food and water consumption, body weight changes; plasma urea nitrogen (BUN), creatinine concentrations and activities of alkaline phosphatase (ALP), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were assayed by time-course experiment. Glutathione S-transferase (GST) and catalase (CAT) activities were also determined in liver tissues on day 5. Distribution of radioactivity in liver, kidney and brain was detected by scintillation spectrometry. The results indicated that uranyl acetate was accumulated in examined tissues, with highest accumulation being in brain. Some of the biochemical biomarkers (BUN, creatinine, ALP) were significantly increased (P<0.05) in the exposure group compared to control animals. Also, BUN and/or creatinine levels and/or ALT and AST activities significantly increased (P<0.01 or P<0.05) with UA exposure on day 3 and/or day 5 compared with results of day 1.     

枳鳖胶囊对大鼠肝纤维化影响的实验研究

目的研究“枳鳖胶囊”抗肝纤维化作用。方法以四氯化碳花生油皮下注射结合高脂饲料、酒水饮料复合因素诱导大鼠肝纤维化模型。以秋水仙碱为对照,观察枳鳖胶囊对肝纤维化大鼠的一般情况,大鼠肝重与脾重,肝功能和肝组织羟脯氨酸(Hyp)含量的影响,并做肝脏病理切片,光镜观察肝组织苏木素伊红(HE)染色网状纤维染色病理形态学改变。结果枳鳖胶囊可明显改善肝纤维化大鼠的精神状态、饮食、毛色泽,增加其体重,抑制其肝脾的增大;显著降低肝纤维化大鼠血清天冬氨酸转氨酶(AST)、丙氨酸转氨酶(ALT),显著升高血清白蛋白(ALb)、白蛋白/球蛋白比值(A/G);降低肝组织Hyp含量;明显减轻大鼠肝细胞损害、肝脏脂肪变性和胶原纤维增生的程度。结论枳鳖胶囊有较好的保护肝细胞,改善肝功能的作用,并能阻止肝纤维化进展甚或逆转肝纤维化病理改变。     

安络化纤丸对大鼠高脂性脂肪肝的治疗作用

目的探讨安络化纤丸对大鼠高脂性脂肪肝的治疗作用。方法以连续饲以高脂饲料(基础饲料加10%猪油、2%胆固醇、0.5%胆酸钠、5%蛋黄)1个月的方法建立高脂性大鼠脂肪肝模型,造模成功后给予安络化纤丸治疗4周,观察一般情况及测定血清丙氨酸氨基转换酶(ALT)、天门冬氨酸氨基转换酶(AST)、总胆固醇(TC)和甘油三酯(TG)水平,测定肝匀浆TG、丙二醛(MDA)及肝组织超氧化物歧化酶(SOD)水平,并对大鼠肝脏行病理学检查。结果安络化纤丸可明显降低高脂性脂肪肝大鼠血清ALT、AST、TC和TG水平,降低肝组织TG含量,提高肝组织SOD活性,并降低肝组织MDA水平。安络化纤丸可显著改善高脂性脂肪肝大鼠肝组织的病理损害。结论安络化纤丸对大鼠高脂性脂肪肝有明显的治疗作用,其作用可能与其抗氧化作用有关。     

安络化纤丸对大鼠酒精性脂肪肝的治疗作用

目的探讨安络化纤丸对大鼠酒精性脂肪肝(AFL)的治疗作用。方法用连续灌服酒精加喂以特制饲料的方法建立大鼠AFL模型,造模成功后给予安络化纤丸治疗4周,观察一般情况及测定血清丙氨酸氨基转换酶(ALT)、天门冬氨酸氨基转换酶(AST)、总胆固醇(TC)和甘油三酯(TG)水平,测定肝匀浆TG、丙二醛(MDA)及肝组织超氧化物歧化酶(SOD)水平,并对大鼠肝脏行病理学检查。结果安络化纤丸可明显降低AFL大鼠血清ALT、AST及TC和TG水平,降低肝组织TG水平,提高肝组织SOD活性,并降低肝组织MDA水平。肝组织病理学研究结果表明,安络化纤丸可显著改善AFL大鼠肝组织的病理损害。结论安络化纤丸对大鼠AFL有一定的治疗作用。